1.4- Dicarbonyl compounds from 2-ethyl-5-methyl

Much more studied is the reaction of /8-dicarbonyl compounds with 2-amino-2-deoxyaldoses in particular, with 2-amino-2-deoxy-D-glu-cose (55), both in neutral and alkaline medium. In neutral methanol or aqueous acetone, 2-amino-2-deoxy-D-glucose reacts with 2,4-pen-tanedione to give52 54 3-acetyl-2-methyl-5-(D-arabino-tetrahydroxy-butyl)pyrrole (56a), and, with ethyl acetoacetate,55 the pyrrole 56b. Similar (tetrahydroxybutyl)pyrroles have been prepared from other /3-keto esters, such as ethyl 3-oxohexanoate, ethyl thiolacetoacetate, and diethyl 3-oxopentanedioate.53,56,56a... 

In the experiments first described, 2-amino-2-deoxy-D-glucose was heated with an excess of the /3-dicarbonyl compound in the absence of solvent. The product so obtained from ethyl acetoacetate, m.p. 142°, [a]n 49.7°, had an analysis corresponding to that for ethyl 2-methyl-5-(D-ara6mo-tetrahydroxybutyl)pyrrole-3-carboxylate and was considered to have this structure (1). In the reaction with 2,4-pentanedione, a material (m.p. 98°, Md — 25.1°) was obtained which was described as 3-acetyl-2-methyl-5-(D-ara5fno-tetrahydroxybutyl)pyrrole (2). Boyer and Furth" repeated the latter reaction, but in methanol solution, and obtained a product, m.p. 133°, whose analytical data were in agreement with those for structure (2). 

Pyrroles.—Formation. A general synthesis of 2-aryl-pyrroles (112) is by cycliz-ation of the esters (111), which are obtained from unsaturated aldehydes and methyl azidoacetate. Thermolysis of the acetylene (113 Ar = p-MeC6H4) gives Al-(p-tolyl)pyrrole with the elimination of p-thiocresol. The pyrrole derivative (115) is the product of the action of benzylamine on tri-(t-butylthio)cyclopropenylium perchlorate (114). Azoalkenes combine with fi-dicarbonyl compounds or with enamines to yield derivatives of Al-aminopyrrole thus the ester (116) and ethyl acetoacetate form (117). The base-catalysed addition of methyl propiolate to toluene-p-sulphonylmethyl isocyanide, T0SCH2NC, gives the ester (118). The dipolar cyclo-adduct (120) of piperidinocyclopentene to the azo-compound (119) forms the A-(tosyl-amino)pyrrole derivative (121) and piperidine on heating. ... 

Indole-3-carboxylate esters and 3-acetylindoles can be prepared by palladium-catalyzed cycli-zation of enamines (14). These can be prepared from the corresponding anilines by condensation with j8-dicarbonyl compounds or by palladium-catalyzed substitution reactions with ethyl acrylate or methyl vinyl ketone <86BCJ927, 90S215>. Overall yields for the two-step process are 60-80% (Scheme 33). 

Cyclocondensation of 3-methyl-l-(5-substituted-3-phenyl-lH-indol-2-ylcarbonyl)-5-(4fi)-pyrazolones with arylidene derivatives of malononitrile using a catalytic amount of triethylamine in refluxing ethanol affords heterocycle [ ]-fused 6-amino-4-aryl-5-cyano-4H-pyrans (14JHC303). Other fused 6-amino-4-aryl derivatives arise from the three-component reaction of benzaldehydes, active methylene compounds (malononitrile/ ethyl cyanoacetate) and 1,3-dicarbonyl compounds catalyzed by 1,8-diaz-abicyclo[5.4.0]undec-7-ene (DBU) in refluxing water (14JHC618). Similar pyrazole[f)]-fused derivatives are obtained from the reaction of benzaldehydes, malonitrile, and 3-substituted-2-pyrazolin-5-ones using sodium... 

In 1967 Shimizu, Sakamoto and Fukushima [13] prepared 2-methyl-4-oxopyrano[2,3-b]pyridine (XIX, R = Me, R = R = H) in 27 per cent yield by condensing ethyl 2-methoxynicotinate with acetone followed by ring closure by heating under reflux with hydroiodic acid. When benzal-dehyde was used instead of acetone, 4-oxo-2-styryl[2,3-b]pyridine (XIX, R = CH CHPh, R = H) was obtained. Spectroscopic data (u.v., i.r. and n.m.r.) are also given for the products [13]. In the same year, Bonsall and Hill [14] reported a number of derivatives of (XIX, R = Me, Ph, C02Et, or CO2H R = R = Me) which they had prepared by the usual Claisen condensation of 3-acetyl-4,6-dimethylpyridine-2-one with appropriate dicarbonyl compounds followed by acid-cyclisations. Overall yields for these compounds were above 30 per cent. Sliwa [15] recently reported the synthesis of (XIX, R = Ph, R = R = H) from ethyl 2-ethoxy-nicotinate. 

Furanones and pyranones constitute a family of compounds that derive from a common a-dicarbonyl intermediate, namely, CHj-CO-CO-(CHOHJn-CHjR (where R-H or OH). Acetylformoin, which has a fruity-caramel aroma, has been isolated from browned instant orange juice (43) and from a sugar model system containing a catalyst (38). It can be formed by dehydration and cyclization of methyl dihydroxy-ethyl reductone (enediol of the methyl dicarbonyl intermediate), but it decomposes easily in air to pungent compounds (44). 

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